Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease

Официальное название

Phase 2 Open Label Prospective Dose-Ranging Clinical Trial With Escalation and Expansion Cohorts to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease

Обзор

This study is a Open Label Prospective Dose-Ranging Escalation and Expansion Trial to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the secondary treatment of acute Graft-versus-Host Disease (aGvHD) in hospitalized patients who are steroid-refractory.

Вмешательства

• Препарат RLS-0071
  RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.

Первичные конечные точки

• Number of participants with treatment-related adverse events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Срок оценки: Day 1 to Day 180]
• Overall Response Rate (ORR) of RLS-0071 [Срок оценки: Day 1 to Day 28]

Вторичные конечные точки (9)

• Incidence of refractoriness (to RLS-0071 +/- ruxolitinib) [Срок оценки: Days 7, 14, 28, 56, and 180]
• Overall corticosteroid use [Срок оценки: Days 7, 14, 28, 56, and 180]
• Initiation of additional or alternative treatment(s) for aGvHD (including an increase in steroid dose to >2 mg/kg methylprednisolone equivalent) [Срок оценки: Day 1 - Day 180]
• Change or shift in Stage for lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD from baseline based on MAGIC Criteria [Срок оценки: Days 7, 14, 28, 56, and 180]
• Attainment of Stage 0 or 1 lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD [Срок оценки: Days 7, 14, 28, 56, and 180]
• Change or shift in overall Grade of aGvHD [Срок оценки: Day 0 - Days 7, 14, 28, 56, and 180.]
• Overall survival [Срок оценки: Day 1 - Day 180]
• Non-relapse mortality [Срок оценки: Day 1 - Day 180]
• Duration of hospital stay [Срок оценки: Day 1 - Day 180]

Критерии участия

Критерии включения

• Male or female adults or adolescents (>12 years old).
• Hospitalized with steroid-refractory aGvHD (grade II-IV) after allo-HSCT
• Anticipated hospital length-of-stay of at least 1 week from the time of RLS-0071 initiation.
• No plans to add additional GvHD treatment medications or to add, dose-adjust, or discontinue GvHD prophylactic medications during the 7-days of RLS-0071 treatment.
• Neutrophil recovery following the stem-cell transplantation, defined as blood neutrophil count >500/mL for at least 3 consecutive measurements and not supported by growth factor supplementation
• Weight ≥40 kg and ≤ 140 kg at screening.

Критерии исключения

• Has received more than 1 allo-HSCT
• Current, previous, or planned use of any systemic treatment in addition to or other than corticosteroids or ruxolitinib for aGvHD
• Previous failure of ruxolitinib treatment
• Uncontrolled GI infection
• Endoscopic and biopsy testing (if performed) that definitively rules out lower GI aGvHD
• Chronic GvHD
• Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.
• Unresolved toxicity or complications (other than aGvHD) due to the allo-HSCT
• Any corticosteroid therapy for indications other than aGvHD at doses of methylprednisolone or equivalent >1 mg/kg per day within 7 days of enrollment.
• Severe organ dysfunction unrelated to underlying aGvHD
• Known hypersensitivity, allergy, or anaphylactic reaction to polyethylene glycol (PEG)
• Significant liver disease that is unrelated to GvHD
• Severe kidney disease
• Currently breast feeding.
• Known pregnancy, a positive pregnancy test at screening, or lactation for WOCBP.
• Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or human immunodeficiency virus (HIV)-1 or HIV-2.
• Active sepsis

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Site 1091 — Duarte
• Site 1343 — Los Angeles
• Site 1318 — Atlanta
• Site 1068 — St Louis
• Site 1100 — Cincinnati
• Site 1382 — Columbus

Испания · 4 центра

• Site 3101 — Seville
• Site 3360 — Madrid
• Site 3227 — Salamanca
• Site 3101 — Seville

Германия · 1 центр

• Site 3242 — Freiburg im Breisgau

Идентификаторы

NCT: NCT06343792 · RLS-0071-203

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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